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Induce pluripotency in fibroblast by synthetic “balance h...

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Posted at 2013-9-24 06:30:59 | All floors |Read mode
Last edited by zhiyuanli In 2013-9-24 07:07 Editor

Background:
The big promise of  induced pluripotency stem cell therapy is to regenerate tissue from stem cells induced from somatic cells. However, most protocols reprogramming somatic cells into pluripotent stem cell has an very low efficiency Other methods, like secondary MEF, can boost the efficiency higher, but its complicated protocol makes it suitable for research but not very applicable for clinical application.
Previously, our collaborators and our lab suggested that the key to restore pluripotency is to achieve “balance” between counter-interacting lineage  specifying forces (see figure). However, “balance” is a dose-dependent and tricky state. With the vast heterogeneity in cell population, it is hard to use a single recipe to restore balance in all cells. This would be a important cause for the low efficiency of reprogramming.

Aim:

Therefore, instead of transfecting constant-expressing  genes, transfecting a synthetic circuits that can compute and restore balance might significantly boosts the reprogramming efficiency, and may be used to other cell fate reprogramming protocols.
Synthetic circuits can be made on plasmid or RNAs; Instead of the traditional methods where all cells receives same treatment, the output from the designed circuit is  cell-specific. the circuit is designed to “sense” the intracellular state, and adjust its output accordingly to reach optimal balance.


Challenges:
In theoretical side: the simplest circuit that can direct another circuit (intrinsic cell state) to a desired state.
In experimental side: whether the synthetic circuit been put on plasmid or RNAs. How to realize the theoretical design.

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